This proposal is a revision of a previously submitted Fogarty International Collaboration Research Award (FIRCA 1 R03 TW05888-01). The proposed study takes advantage of the economy of the screening and follow-up of older adults participating in a project sponsored by the Mexican Institute of Social Security and the Mexican Institute of Psychiatry and will enhance the ability to study depression and cognition among older primary care patients. Our proposed study will add genotyping for APOE, a susceptibility gene for Alzheimer's disease, to the assessments of 3,000 older Mexicans who will be followed for 5 years, to address how APOE genotype and cognitive functioning assessed at baseline are related to the form and course of depressive symptoms and cognitive impairment in older primary care patients. We will compare our findings with a similar survey being carried out in the United States (The "Spectrum survey"; the parent study NIMH MH62210-01). The specific aims of this study to be carried out in primary care settings in Mexico are: 1 to evaluate the extent to which the epsilon4 allele of the Apolipoprotein E gene modifies the association of depressive symptoms with executive and cognitive impairment over the follow-up period; and, 2 to assess whether the effect modification of the association between depressive symptoms and executive and cognitive functioning by the e4 allele of the Apolipoprotein E gene is consistent across ethnic groups (African-Americans, whites living in the United States, and Mexicans). Our Mexican collaborators have contributed to the preparation of this FIRCA and we have met in Philadelphia and Mexico City to consider the response to the reviewers' comments. The proposed work will contribute to the knowledge of the role of APOE in cognition and depression among older Mexicans and will provide the impetus for the development of new research capacity in Mexico that will enhance the ability to do population-based research on genetics.